Researchers from the Medical Research Council (MRC) Cancer Unit at the University of Cambridge have identified a genetic signature related to metabolism associated with poor patient prognosis. The results of the analysis of 8,161 tissue samples could in the future help clinicians decide how best to treat a patient as well as aid the development of new targeted treatments.
For cancer cells to grow and spread they undergo a complex metabolic transformation. This allows the cells to meet the energy needs for the cancer to proliferate. Increasing our understanding of the genes that underpin the changes to metabolic pathways will provide further insight into the events that lead to the spread of cancer within the body.
To this end, Dr Christian Frezza, programme leader, and Edoardo Gaude, a PhD student, from the MRC Cancer Unit, analysed the expression of metabolic genes across 20 different solid cancer types from 8,161 tumour and non-cancerous samples held in The Cancer Genome Atlas (TCGA).
The researchers found that genes related to the OXPHOS pathway - a metabolic pathway in the cell's mitochondria that provides energy to the cell - were significantly down-regulated in the tumour cells from patients with poor clinical outcome. Furthermore, suppression of OXPHOS genes was linked to metastasis, where the cancer spreads to other parts of the body and is linked to even poorer prognosis. Although the link between OXPHOS genes and cancer survival has been found only to be an association at this stage, these results suggest that mitochondrial function might play an important role in metastasis and, therefore, patient prognosis.
Further work is needed to validate these results and to assess to what extent mitochondrial dysfunction contributes to the malignancy of cancer cells.
Dr Christian Frezza said: "Cellular metabolism is known to be a key part of cancer progression. In our work we used data on patient's prognosis to identify a genetic signature related to metabolism that correlated with poor clinical outcome. Using this information, it could be possible in the future to tailor treatments specific to patients. This genetic signature also gives a new target for the development of drugs that could prevent a cancer from spreading throughout the body."
Dr Adam Babbs, research programme manager for cancer at the MRC, said: "The work will inform future patient stratification efforts and demonstrates the important links between metabolism and cancer. Further validation of this work may allow us to predict with greater accuracy a patient's long term survival and design a treatment strategy personalised to improve their chances of living longer."
The study was published in Nature Communications.
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Paper details: Tissue-specific and convergent metabolic transformation of cancer correlates with metastatic potential and patient survival. Gaude and Frezza. Nature Communications. Paper will be available at the following URL after embargo lifts: http://dx.
The MRC Cancer Unit forms part of the School of Clinical Medicine at the University of Cambridge. The Unit undertakes world-leading research into understanding how cancers develop, and seeks to translate this knowledge into new approaches for diagnosis and treatment that can be applied in the clinic. Its focus is on discovering the early steps in epithelial carcinogenesis, because better understanding of these steps will lead to new methods to improve the care and survival of patients with epithelial malignancies such as pancreatic, oesophageal, lung, breast and skin cancers.
The Medical Research Council is at the forefront of scientific discovery to improve human health. Founded in 1913 to tackle tuberculosis, the MRC now invests taxpayers' money in some of the best medical research in the world across every area of health. Thirty-one MRC-funded researchers have won Nobel prizes in a wide range of disciplines, and MRC scientists have been behind such diverse discoveries as vitamins, the structure of DNA and the link between smoking and cancer, as well as achievements such as pioneering the use of randomised controlled trials, the invention of MRI scanning, and the development of a group of antibodies used in the making of some of the most successful drugs ever developed. Today, MRC-funded scientists tackle some of the greatest health problems facing humanity in the 21st century, from the rising tide of chronic diseases associated with ageing to the threats posed by rapidly mutating micro-organisms. http://www.